The present invention relates to a method of determining whether a subject has been exposed to ionizing radiation, to a biological indicator, particularly a nucleic acid indicator, used in such a determination, and to a method of identifying biological indicators useful in detecting exposure to ionizing radiation.
The potential consequences of exposure to ionizing radiation make a biological indicator of past radiation exposure highly desirable. But conventional approaches in this regard have limited the available evidence of past exposure largely to gross pathology or circumstantial evidence, such as telangiectasia (new vessel) formation, fibrosis of skin or other organs, alopecia, cataract formation, sterilization, and teratogenesis (birth defects) in subjects in the first trimester of pregnancy at the time of exposure.
Molecular evidence of prior irradiation has been quite limited. For example, chromosome 2-specific deletions have been identified in hematopoietic cells of CBA/Ca mice that develop leukemia following exposure to an inducing dose of 200 cGy of ionizing radiation. The CBA/Ca mice develop a series of chromosomal abnormalities.
While specific chromosomal changes reproducibly have been demonstrated in hematopoietic cells, there has been no report that gamma irradiation exerts other detectable effects on the hematopoietic stem cells either directly or indirectly, for example, through effects on cells of the bone marrow stromal microenvironment.
Short-lived biochemical indicators also have been reported. For example, increased expression of mRNA for c-jun, c-fos and p53 has been observed in cell cultures following exposure to ionizing radiation. The increased expression is transient, with levels returning to normal as quickly as one hour after exposure. Similarly, elevated circulating levels of the protein TGF-.beta. have been observed in patients exposed to at least 3000 cGy of x-rays in radiotherapy. In patients that do not develop pneumonitis, this level returns to normal by the end of radiotherapy, while in most patients developing pneumonitis, the elevated levels persisted by the end of therapy. In addition, expression of TGF-.beta. varies from individual to individual.
Both the brevity of the TGF-.beta. elevation and the variation in its expression from individual to individual renders the elevation unsuitable as an indicator of past exposure. Indeed, no biological indicator has been reported that is detectable weeks or months following exposure.
A persistent, detectable indicator of past exposure to ionizing radiation would be valuable both in basic radiation biology and in forensic pathology. The need is evident particularly in circumstances where a prior history of radiation exposure is not suspected or is questioned as the etiological agent of a given pathological condition.